These studies will continue our investigations of proliferation and differentiation of hematopoietic stem cells. We have shown that x-ray and alkylating agents not only kill cells, but that this pattern of differentiation of surviving stem cells is altered with erythropoiesis being suppressed. Our studies of hematopoietic stem cells with x-ray or alkylating agents indicate changes in response of such cells as a function of their position in the cell cycle. Such studies were made using hydroxyurea synchronization. These studies on differentiation and response to cytotoxic agents in partially synchronized populations and the possible repair of such damage will be measured using other classes of cytotoxic agents in use clinically. Agents to be studied include procarbazine, and the vinca alkaloids. Quantitative studies of the effects of x-irradiation on the ability of hematopoietic tissues to support clonal growth will also be continued during this next year. This will study both bone marrow and spleen using the spleen colony method.